The components of tachyphylaxis in the cAMP response to beta-adrenergic agonists by C-6 astrocytoma will be characterized. The components of tachyphylaxis include an induction of cyclic nucleotide phosphodiesterase and decreased hormone stimulated adenylate cyclase activity. Once the phosphodiesterase and receptor-adenylate cyclase changes are characterized in astrocytoma cells their significance in brain function will be analyzed. Induction of cyclic nucleotide phosphodiesterase will also be evaluated in human leukocytes. Another phase of the project will study cAMP mediated protein phosphorylation in intact cells. The goal of these experiments is to enumerate the phosphoproteins which are either phosphorylated or dephosphorylated as a result of cAMP action. Subcellular fractionation will then be employed to assign the relevant phosphoproteins to subcellular compartments. Once the subcellular compartmentation is understood, individual proteins will be studied to determine the function of each.